COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study

Jérôme Avouac (1) , Elodie Drumez (2) , Eric Hachulla (3, 4) , Raphaèle Seror (5) , Sophie Georgin-Lavialle (6) , Soumaya El Mahou (7) , Edouard Pertuiset (8) , Thao Pham (9) , Hubert Marotte (10, 11, 12) , Amélie Servettaz (13) , Fanny Domont (14) , Pascal Chazerain (15) , Mathilde Devaux (16) , Pascal Claudepierre (17) , Vincent Langlois , Arsène Mekinian (18) , Alexandre Thibault Jacques Maria (19, 20) , Béatrice Banneville (14) , Bruno Fautrel (14) , Jacques Pouchot (21) , Thierry Thomas (22, 11) , René-Marc Flipo (23) , Christophe Richez (24, 25) , Florence Aeschlimann , Christian Agard , Nassim Ait-Abdallah , Jean-David Albert , Didier Alcais , Jean-Sébastien Allain , Yannick Allanore , Blanca Amador-Borreiro , Zahir Amoura , Emma Andre , Anaïs Arbault , Jean-Benoît Arlet , Laurent Arnaud , Denis Arniaud , Herliette Arty-Hue , Lucie Atlan , Alexandra Audemard-Verger , Christine Audoin-Pajot , Victor Audren , Maxime Bach-Bunner , Hélène Bacquet-Deschryver , Brigitte Bader-Meunier , Nathalie Balandraud , Jean-Charles Balblanc , Stéphane Bally , Frédéric Banal , Pierre Barbery , Thomas Barnetche , Audre Barrelet , André Basch , Vincent Baumier , Guillaume Bayer , Sophie Bayle , Catherine Beauvais , Rudie Beinat , Véronique Belin , Rakiba Belkhir , Ruben Benainous , Alexandre Belot , Mohammed Benammar , Mathilde Benhamou , Ygal Benhamou , Ahmed Benmansour , Pascal Bennet , Brigitte Bernoux-Manat , Elise Berthet , Emilie Berthoux , Ewa Bertolini , Adrien Bigot , Aurélia Bisson-Vaivre , Gilles Blaison , Gilles Bolla , Olivier Bonidan , Christine Bonnet , Raphaël Borie , Marie Bossert , Laurence Boudou , Françoise Bouhour , Kévin Bouiller (26, 27) , Bastien Bouldoires , Karima Boussoualim , Eric Bouvard , Regine Brondino , Pierre Buchlin , Laurence Cabantous , Patrice Cacoub , Simon Cadiou , Maurizio Carteni , Aurélia Carbasse , Brice Castel , Pascal Cathebras , Hervé Caumont , Annalisa Celant , Benjamin Chaigne , Benoît Chaillous , Romuald Champy , Agnès Charcot , Pierre Charles , Isabelle Charlot-Lambrecht , Caroline Charpin , Emmanuel Chatelus , Bernard Chaudier , Pascale Chertok , Xavier Chevalier , Maxime Chevreau , Emilie Chotard , Delphine Chu Miow Lin , Gaëlle Clavel , Cyril Clavel-Osorio , Fleur Cohen , Gregory Cohen , Marie-Eve Colette-Cedoz , Nived Collercandy , Antoine Colombey , Chloé Comarmond , Bernard Combe , Céline Comparon , Elodie Constant , Pascal Coquerelle , Justine Corli , Clémence Corre , Nathalie Costedoat-Chalumeau , Marie Couret , Natacha Courvoisier , Fabienne Coury-Lucas , Cécile Coutarel , Fabrice Coutier , Richard Damade , Laurence Daver-Malaterre , Sarahe Dehimat , Michel Delahousse , Emilie Barrois-Delattre , Delphine Denarie , Camille Deprouw , Emanuelle Dernis , Alban Deroux , Renaud Desbarbieux , Elise Descamps , Chantal Deslandre , Marie Desmurs , Jacques Despaux , Marie Desplats , Frédérick Detree , Valérie Devauchelle-Pensec , Robin Dhote , Philippe Dieude , Yannick Dieudonne , Elisabeth Diot , Guillaume Direz , Djamal-Dine Djeddi , Sarah Douvier , Béatrice Drouet , Catherine Duc , Angélique Ducornet , Carine Dufauret-Lombard , Alain Duhamel , Cécile Dumaine , Anne-Elisabeth Dumel , Chantal Dumoulin-Richez , Agnès Duquesne , Géraldine Durand , Mariane Durandin-Truffinet , Pierre-Marie Duret , Maïka Duval , Mikaël Ebbo , Esther Ebstein , Andra Economu-Dubosc , Stéphanie Emilie , Romain Euvrard , Philippe Evon , Sylvie Fabre , Dorothée Fagedet , Meryem Farhat , Marion Fauconier , Jacques Fechtenbaum , Renaud Felten , Fanny Fernandes , Nicole Ferreira-Maldent , Elodie Feurer , Amandine Fichet , Françoise Flaisler , Nans Florens , Violaine Foltz , Elisabeth Fontanges , Jennifer Foret , Anne-Claire Fougerousse , Anne Fouque-Aubert , Catherine Foutrier-Morello , Hélène Francois-Pradier , Léa Frantzen , Pierre Fritz , Antoine Froissart , Jean Fulpin , Piera Fuzibet , Francis Gaches , Laurence Gagneux-Lemoussu , Mélanie Penhoat-Gahier , Joris Galland , Frédérique Gandjbakhch , Nicole Garnier , Thomas Garraud , Jean-François Garrot , Romain Gastaldi , Véronique Gaud-Listrat , Maud Gauthier-Prieur , Dana Georgescu , Nathalie Gerard , Elisabeth Gervais , Christelle Gibert , Eric Gibert , Ghislaine Gill , Jérôme Gillard , Mélanie Gilson , Pauline Gimonnet , Jeanine-Sophie Giraudet-Le Quintrec , Aude Giraud-Morelet , Baptiste Glace , Camille Glanowski , Bertrand Godeau , Bruno Gombert , Camille Gonnet-Gracia , Tiphaine Goulenok , Philippe Goupille , Olivier Gourmelen , Sophie Govindaraju-Audouard , Franck Grados , Martine Grall-Lerosey , Bruno Grardel , Anne Grasland , Gilles Grateau (6, 28) , Monica Groza , Constance Guillaud , Séverine Guillaume , Caroline Guillibert , Xavier Guillot , Philippe Guilpain (19, 20) , Aline Gury , Marie-Hélène Guyot , Cécile Hacquard-Bouder , Marie-Noelle Havard , Jean-Pierre Hellier , Pascal Hennequin , Basile Henriot , Julien Henry , Véronique Hentgen , Marion Hermet , Muriel Herasse , Julie Hernandez , Miguel Hie , Pascal Hilliquin , Olivier Hinschberger , Ambre Hittinger-Roux , Jan Holubar , Christophe Hudry , Serge Huguenel , Clara Jaccard , Jean-Michel, Jacquemier , Bénédicte Jamard , Catherine Jan , Sylvie Jean , Mathieu Jouvray , Pierre-Antoine Juge , Laurent Juillard , Denis Jullien , Anna Kabala , Abdelkrim Kabchou , Ludovic Karkowski , Françoise Karman , Farid Kemiche , Jérémy Keraen , Pierre Kieffer , Isabelle Kone-Paut , Abdeldajallil Koreichi , Marie Kostine , Sylvain La Batide Alanore , Pierre Lafforgue , Sophie Lahalle , Marc Lambert (29) , Isabelle Lambrecht , Sylvain Lanot , Aurélia Lanteri , Jean-Paul Larbre , Augustin Latourte , Christian Lavigne , Sophie Le Guen Guegan , Guillaume, Le Guenno , Diane Leguy , Agnès Lebrun , Emmanuel Ledoult , Nathalie Legoupil , Erick Legrand , Charlotte Lejeune , Olivier Leloire , Christophe Leroux , Rémi Leroy , Marie Leroy-Gouix , Tifenn Leturcq , Amélie Leurs , Céline Leveque-Michaud , François-Xavier Limbach , Frédéric Liote , Anne Lohse , Pierre Lozac'H , Virginie Lucas , Aurélie Madelon , Nadine Magy-Bertrand , Matthieu Mahevas , Hélène Maillard , Thibault Maillet , Sandrine Malochet-Guinamand , Quentin Mangon , Sylvie Marchou-Lopez , Nathalie Margarit , Thierry Marhadour , Xavier Mariette , Claire Martin , Alexis Mathian , François Maurier , Frédéric Maury , Betty Mazet-Guillaume , Arnaud Mazouyez , Hassan Mazyad , Nadia Mehsen-Cetre , Ulrich Meinzer , Isabelle Melki , Laurent Messer , Corinne Miceli , Martin Michaud , Catherine Michel , Matthias Michel , Mathilde Michon , Anne-Marie Milesi-Lecat , Anna Molto , Marie Moly , Olivier Moranne , Gautier Morel , Hugo Morel , Jacques Morel , Franck Morin , Laurence Moulinier , Guillaume Moulis , Bertrand Moura , Minh Nguyen , Sabine Nicolas-Vullierme , Hubert Nielly , Gaétane Nocturne , Aurore Nottez , Henri-Olivier Ollagnon , Isabelle Pacaud-Vitoux , Anne Pagnier , Caroline Paris , Antoine Parrot , Tristan Pascart , Yasmina Pascaud-Mansour , Lætitia Paulin , Stephan Pavy , Laurent Perard , Yves-Marie Pers (19, 20) , Micheline Pha , Maud Pichon , Audrey Pierreisnard , Gabrielle Pizana , Sylvaine Poignant , Elsa Poix , Agnès Portier , Antoine Poulet , Samira Plassard , Grégory Pugnet , Déborah Puyraimond-Zemmour , Pierre Quartier-Dit-Maire , Marion Quenet , Viviane Queyrel , Loïc Raffray , Philippe Remy , Myriam Renard , Jessica Rene , Sabine Revuz , Bénédicte Rey , Gaëlle Richard-Colmant , Etienne Riviere , Sébastien Riviere , Sophie Robin , Julien Rohmer , Isabelle Roitg , Mélanie Romier , Michel Rolland , Mélanie Roriz , Carole Rosenberg , Linda Rossi , Olivier Roth , Sid-Ahmed Rouidi , Mathilde Roumier , Mickaël Rousiere , Clémentine Rousselin , Bénédicte Rouviere , Christian Roux , Fabienne Roux , Marielle Roux , Nicolas Roux , Diane Rouzaud , Sylvie Rozenberg , Isabelle Sacco , Fatiha Sadji , Laurent Sailler , Carine Salliot , Jean-Hugues Salmon , Alain Saraux , Jean Schmidt , Julie Seguier , Jérémie Sellam , Eric Senbel , Thomas Sene , Patricia Senet , Pascal Seve , Aurélie Sicaud , Perrine Smets , Vincent Sobanski , Christelle Sordet , Elisabeth Sornay-Rendu , Odile Souchaud-Debouverie , Lætitia Sparsa , Lionel Spielmann , Sarah Steib , Chloé Stavris , Catherine Straus , Victor Strotz , Paulina Szafors (19) , Séverine Taffignon-Clave , Justine Simoens , Claire Theillac , Nora Tenenbaum , Benoît Thomachot , Nathalie Tieulie , Soizic Tiriau , Alice Tison , Eric Toussirot , Ludovic Trefond , Sophie Trijau , Sébastien Trouillier , Anne-Priscille Trouvin , Marie-Elise Truchetet , Marc Ulrich , Jacques Vaquier , Eric Veillard , Laurent Veillon , Guillaume Vial , Jean-François Viallard , Judith Victor , Claire Vidon , Mathias Vidon , Camille Vigne , Alexandre Virone , Ursula Warzocha , Daniel Wendling , Claude Werle , Cécile Wibaux , Alexandra Willems , Michel Wisniewski , Juliette Woessner , Bernadette Xerri-Campano

1 Service de rhumatologie [CHU Cochin]
2 METRICS - Evaluation des technologies de santé et des pratiques médicales - ULR 2694
3 Service de médecine interne [Lille]
4 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
5 IMVA - U1184 - Immunologie des Maladies Virales et Autoimmunes
6 CHU Tenon [AP-HP]
7 Centre Hospitalier Tourcoing
8 Centre Hospitalier René Dubos [Pontoise]
9 APHM - Assistance Publique - Hôpitaux de Marseille
10 SAINBIOSE - Santé Ingénierie Biologie Saint-Etienne
11 LBTO - Biologie Intégrative du Tissu Osseux
12 CIC-EC 1408 - Centre d'Investigation Clinique - Epidémiologie Clinique [CHU Saint-Etienne]
13 Hôpital universitaire Robert Debré [Reims]
14 CHU Pitié-Salpêtrière [AP-HP]
15 Groupe Hospitalier Diaconesses Croix Saint-Simon
16 Centre hospitalier intercommunal de Poissy/Saint-Germain-en-Laye - CHIPS [Poissy]
17 EpiDermE - Epidemiology in Dermatology and Evaluation in Therapeutics
18 CHU Saint-Antoine [AP-HP]
19 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
20 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
21 HEGP - Hôpital Européen Georges Pompidou [APHP]
22 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
23 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
24 CHU Bordeaux
25 CIRID - Composantes innées de la réponse immunitaire et différenciation
26 LCE - Laboratoire Chrono-environnement (UMR 6249)
27 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
28 U933 - Maladies génétiques d'expression pédiatrique
29 RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167

Background: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases.Methods: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609.Findings: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53).Interpretation: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases.

Domaines: Microbiologie et Parasitologie

Jérôme Avouac, Elodie Drumez, Eric Hachulla, Raphaèle Seror, Sophie Georgin-Lavialle, et al.. COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study. The Lancet Rheumatology, 2021, 3 (6), pp.e419-e426. ⟨10.1016/S2665-9913(21)00059-X⟩. ⟨hal-03365306⟩